Between a rock and a hard place: Conundrums in the management of cerebral sinovenous thrombosis (CSVT) in children with acute lymphoblastic leukemia (ALL)/lymphoma

Abstract

Background: Anticoagulation therapy (ACT) for CSVT in patients (pts) receiving antileukemic therapy is challenging, especially in presence of a bleed or at risk for coagulopathy. Aims: To describe ACT and outcomes of CSVT in pts receiving asparaginase-( ASP)-based chemotherapy. Methods: Diagnosis, therapy, and outcome data of pts consecutively diagnosed with CSVT at the two participating centers between 2000- 2014 were collected. ACT and CSVT imaging protocols were in place in both centers. Ethics approval was obtained with consent waiver. Results: Thirty-three pts [mean (range) age: 9.1 (2-18) years, 20 boys] had CSVT; 7/33 (21%) presented with intracerebral hemorrhage. Thirty-two pts (96%) received ACT [unfractionated/low molecular weight heparin (LMWH) (16), LMWH alone (16)] at a mean of 1.3 (0- 27) days after CSVT diagnosis. Mean ACT duration was 7 (1-18) months. ACT associated bleeding occurred in 2 pts; 1 major (bleed at diagnosis) and 1 minor (no prior bleed). CSVT progressed in 7 (21%) pts; 5 in first 2 weeks. Two of 7 pts with initial bleed had progression compared to 5 of 25 without bleed (P = 0.63). Progression was associated with chemotherapy phase (ALL Induction 37% vs. post-induction 6%, P = 0.04). Radiological complete/near complete resolution was attained in 22/32 (69%) pts [mean time: 3.7 (1-11) months]. No CSVT-related deaths occurred and 5 (15%) pts had neurologic sequelae. ASP data were missing for 3 pts; 1 had completed ASP prior to CSVT. Of remaining, 24/29 (83%) had ASP re-instated with LMWH without CSVT progression and 5 discontinued (2 CSVT-related, 3 other). Conclusion: In children receiving myelosuppressive therapy, ACT-associated major bleeding (3%) is comparable to that reported in literature for CSVT in children, and ACT resulted in resolution of CSVT in 69% pts. CSVT diagnosis during induction therapy is associated with higher risk of progression indicating the need for optimization of ACT during this phase of antileukemic therapy. ASP therapy can be safely re-instated with concurrent ACT.L719459102015-07-21 <br />